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IntroductionHospitalisations relating to acute respiratory deteriorations (ARD) in Interstitial Lung Disease (ILD) have poor outcomes. Factors predicting adverse outcomes are not fully understood and data addressing the use of illness severity scores in prognostication are limited.ObjectiveTo investigate the use of CURB-65 and NEWS-2 severity scores in the prediction of mortality following ARD-ILD hospitalisation, using prospective methodology and to validate previously determined cut-offs, derived from a retrospective study cohort.MethodsA dual-centre prospective observational cohort study of all adults (≥18y) hospitalised with ARD-ILD in Bristol, UK (n=179). Gender-Age-Physiology (GAP), CURB-65 and NEWS-2 scores were calculated for each eligible admission.Receiver operating characteristics (ROC) curve analysis was used to quantify the strength of discrimination for NEWS-2 and CURB-65 scores. Univariable and multivariable logistic regression analyses were performed to explore the relationship between baseline severity scores and mortality.ResultsGAP showed some merit at predicting 30-day mortality (AUC=0.64,P=0.015); whereas CURB-65 showed modest predictive value for in-hospital (AUC=0.72,PPPPConclusionNEWS-2 has good discriminatory value for predicting in-hospital mortality and moderate discriminatory value for predicting 90-day mortality. The optimal NEWS-2 cut-off value determined was the same as in a previous retrospective cohort, confirming the NEWS-2 score shows promise in predicting mortality following ARD-ILD hospitalisation.

Background: Physical activity during childhood is associated with multiple short- and long-term health benefits. Physical activity levels decline throughout primary school emphasising a need for effective strategies to promote more activity in children. Children have rarely been involved in the intervention development process. This gap is an important omission and there is much to be learnt from existing qualitative studies with children, which could serve as a starting point for specific projects. This systematic review aimed to synthesise qualitative studies with primary school children in the United Kingdom to identify children’s perspectives on why physical activity is important, the factors that influence their physical activity and what they like when it comes to physical activity. Methods: A search of seven databases (conducted in October 2019) identified 26 papers for inclusion. Data extraction and synthesis were conducted using qualitative thematic synthesis. The quality of papers was assessed using the Critical Appraisal Skills Programme checklist for qualitative research. Results: Across the diverse range of studies, several key themes were identified in relation to the three research questions. Children have a comprehensive understanding of the various benefits of physical activity, including benefits for health, fitness and skills development. A range of social agents and practical issues influence children’s physical activity, with friend and peer influences being particularly salient. Most children like to have choice over the activities they undertake and the opportunities for creative physical play such as making up active games. Conclusions: The findings suggest that future interventions should utilize peer relationships, ensure a variety of activities are offered to cater to a broad range of children’s physical activity preferences and incorporate child-led activities where possible. The included studies also highlight a need for more diversity in qualitative research in this area, particularly in terms of ethnicity and age, and combining traditional qualitative methods with creative methods, such as photography, may provide richer insights than when using a single mode of data collection. We also highlight several methodological challenges, and in particular, the need for greater acknowledgement of the role of the researcher in qualitative work with children.

Background:On Dec 8, 2020, deployment of the first SARS-CoV-2 vaccination authorised for UK use (BNT162b2 mRNA vaccine) began, followed by an adenoviral vector vaccine ChAdOx1 nCoV-19 on Jan 4, 2021. Care home residents and staff, frontline health-care workers, and adults aged 80 years and older were vaccinated first. However, few data exist regarding the effectiveness of these vaccines in older people with many comorbidities. In this post-implementation evaluation of two COVID-19 vaccines, we aimed to determine the effectiveness of one dose in reducing COVID-19-related admissions to hospital in people of advanced age.Methods:This prospective test-negative case-control study included adults aged at least 80 years who were admitted to hospital in two NHS trusts in Bristol, UK with signs and symptoms of respiratory disease. Patients who developed symptoms before receiving their vaccine or those who received their vaccine after admission to hospital were excluded, as were those with symptoms that started more than 10 days before hospital admission. We did logistic regression analysis, controlling for time (week), sex, index of multiple deprivations, and care residency status, and sensitivity analyses matched for time and sex using a conditional logistic model adjusting for index of multiple deprivations and care residency status. This study is registered with ISRCTN, number 39557.Findings:Between Dec 18, 2020, and Feb 26, 2021, 466 adults were eligible (144 test-positive and 322 test-negative). 18 (13%) of 135 people with SARS-CoV-2 infection and 90 (34%) of 269 controls received one dose of BNT162b2. The adjusted vaccine effectiveness was 71·4% (95% CI 46·5–90·6). Nine (25%) of 36 people with COVID-19 infection and 53 (59%) of 90 controls received one dose of ChAdOx1 nCoV-19. The adjusted vaccine effectiveness was 80·4% (95% CI 36·4–94·5). When BNT162b2 effectiveness analysis was restricted to the period covered by ChAdOx1 nCoV-19, the estimate was 79·3% (95% CI 47·0–92·5).Interpretation:One dose of either BNT162b2 or ChAdOx1 nCoV-19 resulted in substantial risk reductions of COVID-19-related hospitalisation in people aged at least 80 years.Funding:Pfizer.

PURPOSE: The purpose of this study was to report the rate of reactivation and structural outcome, after the laser or bevacizumab treatment for aggressive posterior retinopathy of prematurity (APROP). METHODS: Retrospective chart review was conducted on consecutive infants with APROP treated with (1) laser or (2) bevacizumab, followed by fluorescein angiography and prophylactic laser to the persistent avascular retina. RESULTS: Thirty-six eyes of 19 patients were included in this study. The mean gestational age was 24.5 weeks with a mean birth weight of 632 g in the bevacizumab group and 24.7 weeks and 777 g in the laser group. Unfavorable outcome occurred in 1 of 22 eyes treated with bevacizumab and in 5 of 14 eyes in the laser group (P = 0.002). Reactivation requiring treatment was common in both groups, 9/22 after bevacizumab and 6/14 after laser (ns). CONCLUSION: Regardless of the initial treatment reactivation requiring retreatment is common in eyes with APROP. The unfavorable structural outcome was significantly more common after initial laser treatment than after initial bevacizumab treatment.

PURPOSE To report reactivation rate after bevacizumab treatment for retinopathy of prematurity (ROP) in eyes with classic ROP (CROP) versus aggressive posterior ROP (APROP) and to report peripheral fluorescein angiography findings in these eyes. METHODS Retrospective chart review was conducted on consecutive infants treated with bevacizumab for ROP, followed by fluorescein angiography and prophylactic laser to persistent avascular retina. RESULTS Sixty-four eyes of 33 patients were included. Mean gestational age was 25 weeks with mean birth weight of 674 g. Mean follow-up was 125 weeks post-menstrual age (PMA). Reactivation requiring treatment after initial bevacizumab was more common in eyes with APROP (8/16) than with CROP (2/48; P < 0.0001). At mean 73 weeks PMA, eyes with APROP had more avascular retina (mean 4.4 disk diameters vs. 2.6 disk diameters; P = 0.0004) and higher percentage of leakage (11/11 eyes vs. 22/38 eyes; P = 0.01) on fluorescein angiography than in eyes with CROP. Unfavorable outcome occurred in 1 of 16 eyes with APROP and in no eyes with CROP. No eye that underwent prophylactic laser after bevacizumab had a poor structural outcome. CONCLUSION In our study, bevacizumab-treated eyes with APROP have a higher likelihood of recurrence and larger area of persistent nonperfusion than in eyes with CROP. Treatment of ROP with bevacizumab followed by prophylactic laser has a low rate of unfavorable structural outcome.

APROP is an uncommon form of ROP. Untreated, eyes with APROP rapidly progress to retinal detachment and blindness. However, early recognition and prompt treatment often allow for effective management. This chapter updates the category of APROP with a more complete discussion including a detailed description of the features, a range of photographic examples, a discussion of more types of APROP, a treatment of diagnostic challenges, and recognition of earlier APROP in order to increase the opportunities for successful treatment. We also discuss the challenges and the alternatives for its practical treatment in order to improve outcomes.

e12062 Background: Prosigna is a standardized test based on the PAM50 gene signature which provides information on intrinsic subtype and risk of recurrence (ROR) score predicting 10y recurrence probability (NanoString Technologies, Inc., Seattle, WA). We evaluated Prosigna’s impact on adjuvant treatment decision beyond immunohistochemistry (IHC) testing. Methods: 125 pre- and postmenopausal EBC patients with ER+, HER2-, pT1-T2 pN0/pN1mi were enrolled (12 centers; 8/2015-11/2016). FFPE specimens were centrally analyzed using Prosigna to classify patients according to the intrinsic tumor subtype and ROR score. The primary endpoint was the impact of the Prosigna test on adjuvant treatment decision. Results: 64% of tumors were classified by PAM50 as Lum A, 35% as Lum B, 0% Basal, 1% HER2-E. The intrinsic subtype concordance between immunohistochemistry (IHC) and Prosigna (n = 119) was 61.3%. In Lum B tumors by IHC the discordance rate was the highest (48% were reclassified as Lum A by Prosigna) as shown in the Table. ROR risk groups were as follows: ROR low (54; 43%), ROR interm. (38; 30%), and ROR high (33; 27%). Prosigna results led to a treatment recommendation change in 49 (39%) patients. In the 76 (61%) cases with the initial recommendation of Hormonal Therapy (HT) alone the final decision changed to chemotherapy (CT)+HT (CHT) in 24 (32%) patients. In the 49 (39%) cases in which the initial recommendation was CHT the final decision changed to HT in 25 (51%) patients. Among the 38 patients with Prosigna intermediate risk, 21 (55%) were allocated to HT. Conclusions: In this prospective decision impact study, Prosigna results led to a 39% change in adjuvant therapy indication. Patients with initial indication of CHT were changed to HT alone in > 50% of cases. Thus, Prosigna results influenced the treatment decisions and reinforced its clinical utility in real-world settings. The intrinsic subtype classification based on IHC didn’t show to be an adequate surrogate for the genomic subtypes as determined by Prosigna. [Table: see text]

10595 Background: To evaluate potential biomarkers of pathological response to bevacizumab-based neoadjuvant therapy in untreated breast cancers (BC) patients recruited in a phase II, multicenter clinical trial. Methods: Patients received a single infusion of bevacizumab (15 mg/ kg) (C1) 3 weeks prior to the beginning of neoadjuvant chemotherapy (NAC) consisting in 4 cycles of docetaxel (60 mg/mq), doxorubicin (50 mg/mq) and bevacizumab (15 mg/ kg) every 21 days (C2-C5) following by surgery. Biomarker expression was assessed by immunohistochemistry (Ki67, CD31, CD31/Ki67, VEGFR2, pVEGFR2 [Y951]) before and after bevacizumab infusion (C1). Gene expression was analyzed using Affimetrix Human Gene ST 1.0. Results: This analysis was performed on 73 patients (49 yr, range 29-70). Twenty (27%) patients obtained best response (G4-G5) whether 50 (68%) were considered as no responder (G1-G2-G3). Response was associated with negative estrogen receptors expression (p=0.02) and high Ki67 basal and after C1 expression (p=0.009 and p=0.01). Six (54%) of the triple negative tumors were responders (p=0.05). Interestingly, change in pVEGFR2 [Y951] staining induced by bevacizumab administration was found significantly associated with response (p=0.0). Decrease in the phosphorilation status of VEGFR2 (Y951) >70% yielded a receiver operating characteristic (ROC) curve area of 0.681 (95% CI: 0.536 - 0.825) with 84% sensitivity and 95% specificity. The positive and negative predictive values for this marker were 60% and 64%, respectively. The change in phosphorilation status of VEGFR2p remains a significant predictor biomarker of response in multivariate analysis (OR=0.9, IC%95 0.96-0.99, p=0.04) after adjusting for clinical-pathological characteristics. Conclusions: These findings suggest the role of the phosphorilation status of VEGFR2 as predictive biomarkers of pathological response to bevacizumab in neoadjuvant setting in breast cancer.

10512 Background: To investigate the role of DCE-MRI versus 18F-Misonidazole (FMISO) positron emission tomography (PET/CT) in the prediction of pathological response to bevacizumab-based neodajuvant therapy. Methods: 73 chemotherapy naïve, stage II and III breast cancer (BC) patients (pts) were enrolled in a phase II, single-arm, multicenter, open-label and prospective clinical trial. Pts received single infusion of bevacizumab (15 mg/ kg) (C1) 3 weeks prior to the beginning of neoadjuvant chemotherapy (NAC) consisting of 4 cycles of docetaxel (60 mg/mq), doxorubicin (50 mg/mq) and bevacizumab (15 mg/ kg) every 21 days (C2-C5), followed by surgery. Tumor proliferation, hypoxia and perfusion were evaluated respectively using 18F-Fluorothymidine (FLT) and 18F-Misonidazole (FMISO) positron emission tomography (PET/CT) and dynamic contrast enhancement magnetic resonance (DCE-MR). Serial imaging studies were performed in parallel at several time points including baseline (BL) and 14-21 days after bevacizumab alone (C1). Results: After only one administration of bev, tumor proliferation and perfusion assessed using FLT-PET and DCE-MRI significantly decrease (-26% and -46%, p10% yielded a ROC curve area of 0.7 (95% CI: 0.56 - 0.85) with high specificity (94%). Conclusions: Our findings suggest a significant value of early changes in tumor hypoxia assessed by FMISO-PET as a biomarker of pathological response in bevacizumab-based neoadjuvant therapy in breast cancer.